MicroRNAs (miRNAs) are a diverse class of highly conserved small RNA molecules that function as critical regulators of gene expression in multicellular eukaryotes and some unicellular eukaryotes. miRNAs are initially transcribed as long primary transcripts (pri-miRNAs) that undergo sequential processing by the RNase III endonucleases Drosha and Dicer to yield the mature ˜20-23 nucleotide species. Mature miRNAs associate with the RNA-induced silencing complex (RISC) and interact with sites of imperfect complementarity in 3′ untranslated regions (UTRs) of target mRNAs. Targeted transcripts subsequently undergo accelerated turnover and translational repression. Importantly, the ability of individual miRNAs to regulate hundreds of transcripts allows these RNAs to coordinate complex programs of gene expression and thereby induce global changes in cellular physiology. Indeed, a growing body of evidence has documented that miRNAs provide functions essential for normal development and cellular homeostasis and accordingly, dysfunction of these molecules has been linked to multiple human diseases.
Cancer causes one in every four US deaths and is the second leading cause of death among Americans. Hepatocellular carcinoma (HCC) is the third-leading cause of death from cancer and the fifth most common malignancy worldwide. HCC is often diagnosed at an advanced stage when it is no longer amenable to curative therapies. Highly active drug-metabolizing pathways and multi-drug resistance transporter proteins in tumor cells further diminish the efficacy of current therapeutic regimens for this cancer type.